Enzymatic desymmetrization of 2,5-dideoxystreptamine precursors

The stereoselective enzymatic acylation of meso-6,7-diazabicyclo[3.2.1]oct-6-ene-2,4-diol 4 and meso-4,6-diazidocyclohexane-1,3-diol 5 in organic media gave the corresponding monoesters in high enantiomeric excess. The hydrolysis of the corresponding diacetate derivatives in the presence of a different set of enzymes provided the same monoesters. The products are precursors of dideoxystreptamine, an aminocyclitol found in synthetic aminoglycoside antibiotics.

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(1R,2R,4S,5S)-2,4-Diazido-5-hydroxycyclohexyl acetateC8H12N6O3Ee ⩾99% (chiral HPLC)[α]D22=+22.0 (c 0.6, CHCl3)Source of chirality: enzymatic desymmetrizationAbsolute configuration: 1R,2R,4S,5S

(1S,2S,4R,5R)-4-Hydroxy-6,7-diazabicyclo[3.2.1]oct-6-en-2-yl acetateC8H12N2O3Ee = 92% (chiral HPLC)[α]D22=-63.3 (c 1.90, CHCl3)Source of chirality: enzymatic desymmetrizationAbsolute configuration: 1S,2S,4R,5R

(1R,2R,4S,5S)-2,4-Diamino-5-hydroxycyclohexyl acetateC8H16N2O3Ee ⩾99%[α]D22=-10.8 (c 0.6, MeOH)Source of chirality: enzymatic desymmetrizationAbsolute configuration: 1R,2R,4S,5S